McLeod syndrome with a novel XK frameshift mutation: A case report

Area of Science:

• Genetics
• Neurology
• Hematology

Background:

• McLeod syndrome (MLS) is a rare X-linked neurohematologic disorder.
• It is caused by loss-of-function mutations in the XK gene.
• Further elucidation of XK gene variations is needed.

Observation:

• A 44-year-old male presented with chorea, cognitive impairment, mental disorders, seizures, peripheral neuropathy, hyperCKemia, and acanthocytosis.
• Family history revealed affected mother and brothers with similar symptoms.
• The patient exhibited classic MLS manifestations.

Findings:

• Whole-exome sequencing identified a novel frameshift mutation (452delA) in the XK gene.
• This mutation leads to premature termination of the XK protein (Gln151ArgfsTer2).
• The patient and a brother were hemizygous, and the mother was heterozygous for the mutation.

Implications:

• This case expands the known spectrum of XK gene mutations in McLeod syndrome.
• Understanding genotype-phenotype correlations in MLS is crucial for diagnosis and management.
• Further research is needed to explain the milder phenotype in the mother.